Reply: Systemic Administration of Adipose-Derived Stromal Cells Concurrent with Fat Grafting.

Abstract

Sir: We would like to thank Dr. Shengyang Jin and Facheng Li for their interest in and thoughtful comments on our article.1 In this study, we investigated the histologic and microenvironmental changes in grafted fat when adipose-derived stromal cells were injected intravenously concurrent with grafting to introduce an adipose-derived stromal cell delivery method, rather than mixing adipose-derived stromal cells with fat. Our findings demonstrate the effects of systemically administered adipose-derived stromal cells in free fat grafting and support the approach as a new clinical strategy. The first issue is finding a protocol for obtaining stromal vascular fraction cells or adipose-derived stromal cells. Although the majority of the studies have used enzymatic digestion method to harvest stromal vascular fraction cells or adipose-derived stromal cells, ethics and safety issues on the use of xenogenic components are continuously increasing.2 As they mentioned, the nonenzymatic digestion methods, such as mechanical isolation and ultrasonic cavitation, could be considered an alternative to circumvent safety issues. However, nonenzymatic digestion methods require further studies with a precisely defined protocol and technical refinement to ensure patient safety and to improve the cell yield.2 The second issue is the proportion of adipose-derived stromal cells in the clinical setting. In an experimental study, 1 g of dry fat contained approximately 8.0 × 105 of stromal vascular fraction cells.3 Thus, a considerable amount of stromal vascular fraction cells could be easily harvested from abundant subcutaneous fat at a low cost in the clinical setting. Although adipose-derived stromal cell supplementation with fat grafting was proven to have an effect on graft volume retention in an experimental study,4 a randomized, placebo-controlled trial,5 a protocol related to the proper ratio of grafted fat and stromal vascular fraction cells or adipose-derived stromal cells in either mixed or systemic delivery of cells remains to be established. Thus, further studies on optimizing the amount and timing of stromal vascular fraction cells or adipose-derived stromal cell injection are required to obtain safe and effective results in fat grafting. The third issue is the time point in observing the angiogenesis and adipogenesis. At postoperative week 1, the distribution of intravenously injected DsRed adipose-derived stromal cells in grafted and subcutaneous fats and in other organs, including the liver, kidney, brain, and heart, and in visceral fat was examined using bioluminescent imaging and immunofluorescent staining (Figs. 2 through 4).1 However, the grafted fat in vascular density was investigated using CD31 staining and graft viability using perilipin staining at postoperative weeks 4 and 8 (Figs. 6 and 8).1 As they mentioned, we agree that analyzing angiogenesis and adipogenesis 1 week postoperatively seems too early. Once again, we thank them for their interest in our article and for raising important issues that need to be discussed. DISCLOSURE The authors have no financial interest to declare in relation to the content of this communication. Ki Yong Hong, M.D., Ph.D.Department of Plastic and Reconstructive SurgeryDongguk University Medical CenterGoyang, Republic of Korea Il-Kug Kim, M.D., Ph.D.Department of Plastic and Reconstructive SurgeryYeungnam University College of MedicineDaegu, Republic of Korea Seong Oh Park, M.D.Department of Plastic and Reconstructive SurgeryHanyang University College of MedicineSeoul, Republic of Korea Ung Sik Jin, M.D., Ph.D.Hak Chang, M.D., Ph.D.Department of Plastic and Reconstructive SurgerySeoul National University College of MedicineSeoul, Republic of Korea